Novel strategies for radioresistant head and neck cancers through targeting the DNA damage response in combination with high-precision proton beam the

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Proton beam therapy (PBT) is increasingly being utilized worldwide for the treatment of specific cancers, such as head and neck squamous carcinoma (HNSCC), as it precisely delivers the radiation dose to the tumour and limits irradiation of surrounding normal tissues. However, there are still significant biological uncertainties of the molecular/cellular effects of PBT due to decreases in energy (increases in ionisation/linear energy transfer) at and around the Bragg peak where the radiation dose is deposited. This consequently leads to significant uncertainties in the use of PBT for the treatment of cancer patients in the clinic. Furthermore, identification of combinational strategies using drugs/small molecule inhibitors that can enhance sensitivity of radioresistant cancers, including subtypes of HNSCC, to PBT are unclear and which maybe distinct from conventional (x-ray) radiation.This MRC-funded DTP studentship will develop novel PBT research investigating key enzymes involved in the cellular DNA damage response (including PARG, ATM, ATR and DNA-Pk), as targets to overcome radioresistance of HNSCC. This will be delivered through the use of established 2D cell lines, 3D spheroids and patient-derived organoids of HNSCC. This project has high translational potential in the establishment of more effective clinical management and treatments for HNSCC patients using PBT.